Adenocarcinoma of the prostate is now recognized as being the most common cancer of adult men in the United States. The increased incidence of this disease has led to heightened awareness by physicians and patients of the importance of early diagnosis. Accompanying this has been an intensification of efforts to develop techniques for screening and identification of early stage lesions. It is recognized, however, that many patients with small, "latent" carcinomas may not need radical therapy since their disease is unlikely to become clinically manifest. A need exists, therefore, for a diagnostic test which can discriminate between those cancers which will progress versus those which will not. This proposal outlines the rationale and methods to explore video image analysis of DNA ploidy, nuclear roundness factor and chromatin texture as potential prognostic tools. Through both retrospective and prospective analysis, histopathologic evaluation of biopsies and radical prostatectomy specimens will be carried out. Whole mount preparations of radical prostatectomy specimens will be used to permit adequate evaluation of histologic grade and tumor volume. Image analysis will be used to 1) detect changes that might be associated with increasing tumor volume, 2) search for microheterogeneity that can occur in a given prostatic tumor, 3) test the hypothesis that image analysis may be more successful at detecting small proportions of hyper 5N cells than is flow cytometry, 4) search for evidence of a "field effect" by examining premalignant abnormalities and multifocal carcinomas, 5) evaluate these markers for their ability to predict response to hormone therapy, 6) determine whether differences occur between carcinomas that arise in the peripheral zone versus those from the transition zone and 7) determine whether or not aneuploid populations of cells that predominate post-radiotherapy can be detected in biopsies taken before treatment begins. By correlating these results with those of the other members of the proposed program project it will be possible to determine their biologic and clinical significance, either alone or in combination with other prognostic markers. In so doing, the eventual goal of the proposal is to provide diagnostic markers that can make meaningful contributions to clinical management decisions in the treatment of this increasingly common neoplasm.